Proteomic Profiling Unraveling the Role of Lactate Dehydrogenase a in Vascular Repair and Functional Recovery after...

Spinal cord injury (SCI) leads to complex pathological cascades, including endothelial cell dysfunction and vascular degeneration. In this study, we employed label-free quantitative proteomics to profile spinal cord tissue following injury, and identify altered molecular pathways. Proteomic analysis identified lactate dehydrogenase A (LDHA) as significantly upregulated at day post-injury 7 (DPI-7) and a potential regulator of vascular endothelial growth factor (VEGF)-VEGFR2 signaling. Pharmacological inhibition of LDHA using FX-11 led to increased oxidative stress in endothelial cells, reduced cell proliferation, impaired angiogenesis, and aggravated neuronal damage at the lesion epicenter. These findings suggest that LDHA functions as a metabolic regulator supporting endothelial cell survival under injury conditions. Notably, systemic lactate treatment counteracted the detrimental effects of LDHA inhibition and promoted functional recovery post-SCI. Overall, this study identifies LDHA as a critical regulator of VEGF-VEGFR2 signaling post-SCI and proposes lactate treatment as a potential therapeutic strategy to enhance vascular repair.